Centre de Recherches des Cordeliers, UMR_S INSERM 1138, Equipe 17, Université Paris Descartes, 15 rue de l'école de médecine, 75006, Paris, France.
APHP, Service de Pathologie de L'Hôpital Cochin-Hôtel-Dieu, Université Paris Descartes, 27 rue du Faubourg Saint-Jacques, 75014, Paris, France.
Graefes Arch Clin Exp Ophthalmol. 2019 Nov;257(11):2401-2427. doi: 10.1007/s00417-019-04462-4. Epub 2019 Sep 16.
This study was conducted in order to study Sostdc1 expression in rat and human developing and adult eyes.
Using the yeast signal sequence trap screening method, we identified the Sostdc1 cDNA encoding a protein secreted by the adult rat retinal pigment epithelium. We determined by in situ hybridization, RT-PCR, immunohistochemistry, and western blot analysis Sostdc1 gene and protein expression in developing and postnatal rat ocular tissue sections. We also investigated Sostdc1 immunohistolocalization in developing and adult human ocular tissues.
We demonstrated a prominent Sostdc1 gene expression in the developing rat central nervous system (CNS) and eyes at early developmental stages from E10.5 days postconception (dpc) to E13 dpc. Specific Sostdc1 immunostaining was also detected in most adult cells of rat ocular tissue sections. We also identified the rat ocular embryonic compartments characterized by a specific Sostdc1 immunohistostaining and specific Pax6, Sox2, Otx2, and Vsx2 immunohistostaining from embryonic stages E10.5 to E13 dpc. Furthermore, we determined the localization of SOSTDC1 immunoreactivity in ocular tissue sections of developing and adult human eyes. Indeed, we detected SOSTDC1 immunostaining in developing and adult human retinal pigment epithelium (RPE) and neural retina (NR) as well as in several developing and adult human ocular compartments, including the walls of choroidal and scleral vessels. Of utmost importance, we observed a strong SOSTDC1 expression in a pathological ocular specimen of type 2 Peters' anomaly complicated by retinal neovascularization as well in the walls ofother pathological extra-ocular vessels. CONCLUSION: As rat Sostdc1 and human SOSTDC1 are dual antagonists of the Wnt/β-catenin and BMP signaling pathways, these results underscore the potential crucial roles of these pathways and their antagonists, such as Sostdc1 and SOSTDC1, in developing and adult mammalian normal eyes as well as in syndromic and nonsyndromic congenital eye diseases.
本研究旨在研究 Sostdc1 在大鼠和人眼发育及成年期的表达。
利用酵母信号序列捕获筛选方法，我们鉴定了编码成年大鼠视网膜色素上皮分泌蛋白的 Sostdc1 cDNA。通过原位杂交、RT-PCR、免疫组织化学和 Western blot 分析，我们确定了 Sostdc1 基因和蛋白在发育中和出生后大鼠眼组织切片中的表达。我们还研究了 Sostdc1 在发育中和成年期人眼组织中的免疫组化定位。
我们发现在发育中的大鼠中枢神经系统（CNS）和眼睛中，Sostdc1 基因在受孕后第 10.5 天（E10.5 dpc）到第 13 天（E13 dpc）的早期发育阶段有明显的表达。在大鼠眼部组织切片的大多数成年细胞中也检测到特异性的 Sostdc1 免疫染色。我们还鉴定了大鼠眼胚胎期的胚胎隔室，这些隔室在 E10.5 至 E13 dpc 的胚胎阶段具有特异性的 Sostdc1 免疫染色和特异性的 Pax6、Sox2、Otx2 和 Vsx2 免疫染色。此外，我们确定了 SOSTDC1 免疫反应性在发育中和成年期人眼眼部组织切片中的定位。事实上，我们在发育中和成年期人类视网膜色素上皮（RPE）和神经视网膜（NR）以及几个发育和成年期人类眼部隔室中检测到 SOSTDC1 免疫染色，包括脉络膜和巩膜血管的壁。最重要的是，我们在 2 型 Peters 异常伴视网膜新生血管化的病理性眼部标本以及其他病理性眼外血管的壁中观察到强烈的 SOSTDC1 表达。
由于大鼠 Sostdc1 和人 SOSTDC1 是 Wnt/β-catenin 和 BMP 信号通路的双重拮抗剂，这些结果强调了这些通路及其拮抗剂（如 Sostdc1 和 SOSTDC1）在发育中和成年期哺乳动物正常眼中以及综合征性和非综合征性先天性眼病中的潜在关键作用。
